The proposed project is to continue to use the technique of microiontophoresis to identify areas in the brain where morphine acts directly to modify neuronal activity which is elicited by a nociceptive stimulus. Such sites are considered to be sites where morphine acts to produce analgesia. To test this possibility the technique of intracerebral (IC) injection of morphine into such areas was used to determine if morphine acts in such a discrete area to produce analgesia. Both of these techniques have been successful in defining the mesencephalic reticular formation (MRF) as a site where morphine appears to act to produce analgesia. In contrast, in some areas of the serotonergic (5-HT) system morphine does not modify changes in neuronal activity elicited by nociceptive stimuli. Morphine produced an inhibition of firing in about 50 percent of the neurons in the serotonergic system. However, this did not appear to be a specific narcotic effect because it was not stereospecific; dextrorphan, the analgesically inactive stereoisomer of levorphanol, a potent morphine agonist, also produced an inhibition of neuronal firing which was indistinguishable from that produced by morphine. One of my goals in the coming year is to study the areas of the serotonergic system located in the brainstem (i.e., raphe magnus, pallidus and obscurus) to determine 1) if the neuronal activity in these areas can be altered by a nociceptive stimulus, and 2) if morphine can block such alteration. My second objective is to determine how morphine blocks the acceleration in neuronal firing, elicited by a nociceptive stimulus, in the MRF. Based on preliminary data it is possible that morphine antagonizes the actions of one or more excitatory neurotransmitters. A third objective is to determine if endorphins and encephalins will also produce analgesia when administered IC into the MRF. BIBLIOGRAPHIC REFERENCES: Haigler, H.J. and Aghajanian, G.K.: Serotonin receptors in the brain. Fed. Proc. (in press), 1977. Mittleman, R.S. and Haigler, H.J.: Analgesia produced by microinjection of morphine into the mesencephalic reticular formation (MRF) of the rat. Fed. Proc. (in press), 1977.